S-531011 + Pembrolizumab for Cancer

(aCCeleR8-001 Trial)

Recruiting at 5 trial locations

Overseen By Shionogi Clinical Trials Administrator Clinical Support Help Line

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shionogi Inc.

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune diseases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 12 months

274 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of Part A is to evaluate the safety and tolerability of S-531011 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of S-531011. The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had systemic anticancer drugs within 28 days before starting the trial, and you should not be on chronic systemic corticosteroids or immunosuppressive agents.

What data supports the effectiveness of the drug Pembrolizumab in treating cancer?

Research shows that Pembrolizumab has been effective in improving survival rates in patients with advanced non-small cell lung cancer and gastric cancer, especially when the cancer cells have certain markers (PD-L1 positive). ^{1 2 3 4 5}

Is the combination of S-531011 and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA or MK-3475, is generally well tolerated in humans, with common side effects including fatigue, rash, itching, and diarrhea. Less common side effects can include inflammation of the thyroid, colon, liver, and lungs. Serious heart-related side effects are rare, occurring in about 1% of cases. ^{6 7 8 9 10}

What makes the drug S-531011 + Pembrolizumab unique for cancer treatment?

The combination of S-531011 with Pembrolizumab is unique because Pembrolizumab is a monoclonal antibody that blocks the PD-1 receptor on T cells, enhancing the immune system's ability to attack cancer cells. This combination may offer a novel approach by potentially increasing the effectiveness of immune responses against cancer compared to using Pembrolizumab alone. ^{11 12 13 14 15}

Research Team

Shionogi Clinical Trials Administrator Clinical Support Help Line

Principal Investigator

Shionogi

Eligibility Criteria

Adults with advanced or metastatic solid tumors without standard treatment options, or those who cannot tolerate such treatments. Participants must have measurable disease, a life expectancy of at least 12 weeks, and good performance status (able to carry out daily activities). They should not have autoimmune diseases requiring steroids, HIV infection, recent major surgery, uncontrolled brain metastases or other cancers within the last 3 years.

Inclusion Criteria

My cancer type is one of those specifically selected for this trial's Part C.

I have one of the specified types of cancer (e.g., melanoma, lung, breast).

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am not pregnant, breastfeeding, or trying to become pregnant.

Known history of severe allergy, hypersensitivity, anaphylaxis, or any serious adverse reaction to any component of study intervention or formulation components and/or any other monoclonal antibodies.

A positive serological test for human immunodeficiency virus (HIV) infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive S-531011 as monotherapy or in combination with pembrolizumab by intravenous infusion

up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• S-531011

Trial Overview The trial is testing S-531011 alone and combined with Pembrolizumab in patients with various types of solid tumors. It aims to find the safest dose that can be given (MTD) and see how well it works against cancer (antitumor activity). The study has multiple parts: determining safe doses and then assessing effectiveness at these doses.

Participant Groups

Group I: Part C: S-531011 + pembrolizumab Experimental Treatment 2 Interventions

Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 12 months.

Group II: Part B: S-531011 Monotherapy Experimental Treatment 1 Intervention

Participants will receive S-531011 at the the RP2D by intravenous infusion for up to approximately 12 months.

Group III: Part A-2: S-531011 + pembrolizumab Experimental Treatment 2 Interventions

Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 12 months.

Group IV: Part A-1: S-531011 Monotherapy Experimental Treatment 1 Intervention

Participants will receive escalating doses of S-531011 by intravenous infusion for up to approximately 12 months.

Who Is Running the Clinical Trial?

Shionogi Inc.

Lead Sponsor

Trials

10

Recruited

760+

Shionogi

Lead Sponsor

Trials

122

Recruited

42,100+

Dr. Isao Teshirogi

Shionogi

Chief Executive Officer since 2008

PhD in Pharmaceutical Sciences from the University of Tokyo

Dr. Takuko Sawada

Shionogi

Chief Medical Officer since 2022

MD from a recognized institution (specific details not found)

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pembrolizumab shows significant efficacy in patients with advanced gastric/gastroesophageal junction cancer who have a combined positive score (CPS) of 10 or higher, demonstrating improved overall survival (OS) and objective response rates (ORR) compared to chemotherapy in multiple trials.

In the KEYNOTE-062 trial, pembrolizumab resulted in a median OS of 17 months compared to 11 months for chemotherapy, indicating a strong potential for this treatment in patients with high CPS, alongside favorable outcomes in progression-free survival (PFS) and duration of response (DOR).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10. Wainberg, ZA., Fuchs, CS., Tabernero, J., et al.[2022]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In the KEYNOTE-010 study, pembrolizumab significantly improved overall survival (OS) compared to docetaxel in patients with advanced non-small cell lung cancer (NSCLC), with 5-year OS rates of 25.0% for pembrolizumab versus 8.2% for docetaxel in patients with PD-L1 TPS ≥50%.

Among patients who completed 35 cycles of pembrolizumab, 83.0% were alive three years after treatment, highlighting its long-term efficacy, and the study supports pembrolizumab as a standard treatment option for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC. Herbst, RS., Garon, EB., Kim, DW., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor known for its antitumor effects, can cause multiple inflammatory adverse events, highlighting the need for awareness of its side effects.

This case emphasizes the importance of early identification of various cutaneous side effects associated with immunotherapy, which can affect patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. Honigman, AD., Lai, F., Elakis, J., et al.[2021]

Pembrolizumab, a monoclonal antibody used for cancer treatment, can cause rare but severe immune-related toxicities, including myocarditis, as demonstrated in a case of an 83-year-old male who developed fatal myocarditis after two doses.

The COVID-19 pandemic complicated the management of these toxicities, as patients and families were hesitant to seek medical care, highlighting the importance of educating patients about potential symptoms and the need for timely reporting to ensure safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report. Elder, CT., Davis, EC., Jaipal, S., et al.[2022]

In the KEYNOTE-061 study involving 371 patients with advanced gastric and gastroesophageal junction cancer, pembrolizumab did not significantly improve overall survival or progression-free survival compared to paclitaxel, indicating limited efficacy in this population.

Health-related quality of life (HRQoL) assessments showed no significant difference between patients receiving pembrolizumab and those receiving paclitaxel, suggesting that both treatments had a similar impact on patients' quality of life during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in advanced gastric/gastroesophageal junction cancer with second-line pembrolizumab in KEYNOTE-061. Van Cutsem, E., Amonkar, M., Fuchs, CS., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, a monoclonal antibody that blocks PD-1, effectively enhances antitumor immune responses and has been approved for treating advanced melanoma, renal cell cancer, and non-small cell lung cancer.

In vivo studies using PET imaging showed that pembrolizumab is stable in circulation and primarily accumulates in the liver and spleen, providing valuable insights into its pharmacokinetics and potential for optimizing dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. England, CG., Ehlerding, EB., Hernandez, R., et al.[2020]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

4. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Five Year Survival Update From KEYNOTE-010: Pembrolizumab Versus Docetaxel for Previously Treated, Programmed Death-Ligand 1-Positive Advanced NSCLC. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

7. England pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Health-related quality of life in advanced gastric/gastroesophageal junction cancer with second-line pembrolizumab in KEYNOTE-061. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

12. United States pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. [2020]

13. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

15. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]